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Title: Prorenin, its maturation and the (pro)renin receptor
Author: L'Huillier, Nathalie
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Expression of the mouse putative (pro)renin receptor (RR) was detected in all tissues and cell lines examined including human mesangial cells previously reported to be negative for RR. Mouse RR was also present during development from E9.5. Phylogenic studies revealed RR is highly conserved between species and likely to be important physiologically. The role of RR was investigated in a rat model in which (pro)renin triggers malignant hypertension (MH). TGR(Cyp1al-Ren2) animals carry a mouse renin gene under the control of the Cyp1a1 promoter inducible by dietary indole-3-carbinol. A rapid rise in blood pressure was accompanied by weight loss and polyuria. The animals exhibited microinfarctions, inflammatory cell infiltration and fibrinoid necrosis in the heart and distal tubule hyperplasia and thickening of intra-renal arterial wall without glomerulosclerosis, in the kidney. To investigate the possible role of RR, a prorenin decoy peptide was used to attempt to ameliorate the MH phenotype in TGR(Cyp1a1-Ren2) animals. This peptide which competes with prorenin for binding to RR, has been shown to improve vascular injuries in diabetic nephropathy. In TGR(Cyp1a1-Ren2), however, no changes in the MH phenotype could be observed, except in the mesentery in which less severe fibrinoid necrosis developed. To complement work on RR, prorenin maturation and renin storage were studied during development. The data showed the complete absence of renin granules in mouse kidneys before birth. Low sodium diet and ACE inhibition triggered (pro)renin granules to be produced in the foetal kidney. Two ACE inhibitors differing in their ability to cross the placenta were used. The data suggest that fetal renin granule formation is under the control of both foetal and maternal RAS. The lack of evidence for regulation of RR in a model of high prorenin and malignant hypertension suggests that the function of this protein may need to be re-assessed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available